Susceptibility to Leishmania major infection in the absence of IL-4

Infection with the intracellular parasite Leishmania major is the prototypi cal model system used to study Th1 and Th2 cytokine responses in vivo. Mous e strains that are resistant to L. major produce high levels of IFN gamma, and Th1 cytokines while susceptible BALB/c mice have elevated levels of IL- 4, and Th2-associated cytokines during infection. While antibody neutraliza tion of IL-4 or IFN gamma in vivo alters the disease patterns, infection of mice genetically deficient for IL-4 or IL-4 receptor (IL-4R alpha) yield s urprising outcomes. Contrary to the Th1/Th2 paradigm, IL-4 -/- and IL-4R al pha -/- mice remain highly susceptible to L. major parasite substrain LV39. In distinct contrast, another L. major substrain, IR173, the IL-4R alpha - /- mice are highly resistant. These findings indicate a disparity between a ntibody treatment versus gene deletion, and more generally, challenge the r ole of IL-4 in promoting susceptibility to L. major. Furthermore, IL-4R alp ha -/- mice reveal that the ability of L. major to escape immune clearance depends on the parasite substrain. (C) 2000 Elsevier Science B.V. All right s reserved.